Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma
Menée sur 98 cas de carcinome rénal à cellules claires, cette étude évalue la fréquence de mutations des gènes de la voie de signalisation de la protéolyse ubiquitine-dépendante
We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of ~1,100 genes in 88 additional ccRCCs, from which we discovered 12 previously unidentified genes mutated at elevated frequencies in ccRCC. Notably, we detected frequent mutations in the ubiquitin-mediated proteolysis pathway (UMPP), and alterations in the UMPP were significantly associated with overexpression of HIF1
α and HIF2α in the tumors (P = 0.01 and 0.04, respectively). Our findings highlight the potential contribution of UMPP to ccRCC tumorigenesis through the activation of the hypoxia regulatory network.